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Min Li,1,* Kun Fan,1,* Bohao Zheng,1,* David Zekria,2 Tao Suo,1 Han Liu,1 Sheng Shen,1 Houbao Liu,1 Xiaoling Ni1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK*These authors contributed equally to this workCorrespondence: Xiaoling Ni; Houbao LiuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 64041998; +86 21 64041997Email ni.xiaoling@zs-hospital.sh.cn; liu.houbao@zs-hospital.sh.cnPurpose: Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies.Materials and Methods: Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo.Results: Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC.Conclusion: SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.Keywords: gallbladder cancer, SLC39A4 (ZIP4), proliferation, migration, potential therapeutic target

Jie Wang,1,* Xiaobo Bo,1,* Pinxiang Lu,2,* Tao Suo,1 Xiaoling Ni,1 Han Liu,1 Hongtao Pan,1 Sheng Shen,1 Min Li,1 Dexiang Zhang,2 Yueqi Wang,1 Houbao Liu1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of General Surgery, Xuhui Central Hospital, Shanghai, China *These authors contributed equally to this work Objective: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. Patients and methods: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan–Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. Results: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0–22.0 vs 8.0, 95% CI: 5.0–11.0 for median OS; 22.0, 95% CI: 13.0–33.0 vs 9.0, 95% CI: 5.0–11.0 for median CSS; both log-rank P

A robust, practical, and sustainable isomerization-suppressed peptide bond formation via acyl sulfonamide, a twisted amide, is disclosed. Tosyl isocyanate and pentafluorobenzyl bromide were applied in combination to activate the peptide C-terminus, which then reacted with an amine to yield an elongated peptide with high stereochemical purity. Careful analysis of NMR spectra of the active intermediate revealed the presence of an intramolecular hydrogen bond, suggesting that the hydrogen bond suppressed Cα-epimerization during amidation. The isomerization suppression by the intramolecular hydrogen bond is expected to be effective even under high dilution conditions, making the present method a powerful tool for the synthesis of complex macrocyclic peptides. In addition to peptide synthesis, the developed synthetic entry to twisted amides can be applied to the investigation of transition metal-catalyzed N-C bond activation. Moreover, the application to the N-C bond activation returned insight into peptide synthesis, leading to the use of sulfonamide as a protecting group of carboxylic acid that can be orthogonally removed in the presence of other conventional protecting groups., (© 2024 Wiley-VCH GmbH.)

A near-miss is a situation in which a gambler almost wins but falls short by a small margin, which motivates gambling by making it feel like success is within reach. Existing research has extensively investigated the influence of contextual information on near-miss outcome processing; however, the impact of reward expectancy has received limited attention thus far. To address this gap, we utilized the wheel of fortune task and event-related potential technique (ERP) to quantify the electrophysiological responses associated with gambling outcomes at different levels of reward expectancy. Behaviorally, near-miss outcomes elicited a greater occurrence of counterfactual thoughts, feelings of regret, and heightened anticipation of rewards for subsequent trials compared to full-miss outcomes. ERP findings indicated that in contrast to full-miss outcomes, near-miss outcomes diminished feedback-related negativities (FRNs) and amplified P300s when reward expectancy was low, but amplified FRNs and diminished P300s when reward expectancy was high. These findings provide valuable insights into the neural mechanisms underlying the processing of outcome proximity and reward expectancy., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Organoids refer to 3D cultures established to recapitulate histology, pathology, architecture, and genetic traits of various organs and tissues in the body, thereby replacing 2D cell cultures, xenograft, and animal models. Organoids form a 3D in vitro mimic of original tissues like the liver and are derived from embryonic or adult tissue stem cells. Liver and bile duct tumor organoids, also called, tumoroids capture genetic diversity, cellular, and pathophysiological properties of original tumors. Moreover, co-culture techniques along with genetic modulation of organoids allow for using tumoroids in liver and bile duct cancer research and drug screening/testing. Therefore, tumoroids are promising platforms for studying liver and bile duct cancer, which paves the way for the new era of personalized therapies. In the current review, we aimed to discuss liver and bile duct organoids with special emphasis on tumoroids and their applications, advantages, and shortcomings., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests, we do not have any possible conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ethnopharmacological Relevance: While the seasonal variations in the human immune function and many infectious diseases are well-known, to develop therapeutic strategies regarding such seasonality is quite challenging. However, some traditional medical practices have already taken the seasonality into account, such as the "Season Tea" (ST) decoctions investigated in the present study., Aim of the Study: We present a study of the ST decoctions from traditional Chinese medicine, which include four formulae designed for the four seasons, aiming to investigate their pharmacological commonality and distinction., Materials and Methods: A rat model of acute pharyngitis was utilized for the pharmacological study, and the effects of the ST decoctions were evaluated through histology, biomedical assays, microarray analysis, real-time quantitative PCR and Western blot., Results: The experimental data show that all of the four ST formulae display good pharmaceutical effects on acute pharyngitis, and circadian rhythm appears to be a significant pathway for investigating their pharmacological commonality and distinction. Specifically, while all of the four ST decoctions can regulate the circadian-rhythm-related genes ARNTL and BHLHE40, the regulation is along different directions with the modification of the supplements and the substrates in each ST formula., Conclusion: These results indicate the correlation between the acute pharyngitis and circadian rhythm, and illustrate the possibility of synergistically and subtly regulating ARNTL and BHLHE40, which is significant for relevant drug development., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a poten ial conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mucormycosis is a significant cause of morbidity and mortality in patients with hematological malignancies, but its characteristics are not fully understood. This study aimed to gain a better understanding of the clinical features of mucormycosis in patients with hematological malignancies in eastern China., Methods: A single-center retrospective analysis was conducted on the demographic profile, microbiology, management, and 90-day mortality of mucormycosis patients with hematological malignancies between 2018 and 2023., Results: A total of 50 cases were included in the study, consisting of 11 proven and 39 probable cases of mucormycosis. The median age of the patients was 39.98 ± 18.52 years, with 52% being male. Among the cases, 46% had acute myeloid leukemia (AML), 16% had acute lymphoblastic leukemia (ALL), and 16% had myelodysplastic syndrome. The most common manifestations of mucormycosis were pulmonary (80%), disseminated (16%), and rhinocerebral (4%). The diagnosis was confirmed through histology, culture, microscopy, and molecular diagnostic techniques. The most commonly identified fungal species were Cunninghamella (40%), Rhizopus (26%), and Rhizomucor (22%). Treatment involved antifungals in 84% of cases and surgery in 10% of cases. The 90-day mortality rate was 76%. Logistic regression analysis revealed that treatment with amphotericin B and surgery was associated with improved survival, while neutropenia and administration of voriconazole prior to diagnosis was associated with higher mortality., Conclusions: Mucormycosis continues to have a high mortality rate in patients with hematological malignancies. Early diagnosis using various techniques, including molecular biology, along with the appropriate use of amphotericin B and surgery when possible, is vital for the successful treatment of mucormycosis., (© 2024. The Author(s).)

This study examines how children attribute moral responsibilities to their past and future actions and what role culture plays in children's temporal moral attribution. A total of 346 U.S. and Chinese 6-7 and 8- to 9-year-old children were randomly assigned to a past or future condition, in which they answered questions about their moral/immoral actions in hypothetical scenarios described as occurring in the last week or the next week. Whereas U.S. 8- to 9-year-olds favored more praise and reward for their future good deeds than past ones, Chinese 8- to 9-year-olds favored more praise and reward for their past good deeds than future ones. Chinese children also moralized their actions to a greater extent than U.S. children, and children reasoned about their moral/immoral actions in line with their cultural beliefs. Interesting age differences also emerged, suggesting the continuing development of mental time travel and moral cognition across middle childhood. The findings shed new light on the important role of time in moral judgment that is constrained by development progressions in mental time travel and specific to the cultural context. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications., Competing Interests: Declaration of competing interest The authors hereby state that there are no financial interests or personal relationships that may have appeared to exert an influence on the research findings presented in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Risk-taking is a common, complex, and multidimensional behavior construct that has significant implications for human health and well-being. Previous research has identified the neural mechanisms underlying risk-taking behavior in both adolescents and adults, yet the differences between adolescents' and adults' risk-taking in the brain remain elusive. This study firstly employs a comprehensive meta-analysis approach that includes 73 adult and 20 adolescent whole-brain experiments, incorporating observations from 1986 adults and 789 adolescents obtained from online databases, including Web of Science, PubMed, ScienceDirect, Google Scholar and Neurosynth. It then combines functional decoding methods to identify common and distinct brain regions and corresponding psychological processes associated with risk-taking behavior in these two cohorts. The results indicated that the neural bases underlying risk-taking behavior in both age groups are situated within the cognitive control, reward, and sensory networks. Subsequent contrast analysis revealed that adolescents and adults risk-taking engaged frontal pole within the fronto-parietal control network (FPN), but the former recruited more ventrolateral area and the latter recruited more dorsolateral area. Moreover, adolescents' risk-taking evoked brain area activity within the ventral attention network (VAN) and the default mode network (DMN) compared with adults, consistent with the functional decoding analyses. These findings provide new insights into the similarities and disparities of risk-taking neural substrates underlying different age cohorts, supporting future neuroimaging research on the dynamic changes of risk-taking., (Copyright © 2024. Published by Elsevier Ltd.)

Abnormal mTORC1 activation by the lysosomal Ragulator complex has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting upregulates RNF152 and mediates the metabolic status of cells. We report that RNF152 regulates mTORC1 signaling by targeting a Ragulator subunit, p18, and attenuates gemcitabine resistance in gallbladder cancer (GBC). We detected levels of RNF152 and p18 in tissues and undertook mechanistic studies using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates RNF152 expression. RNF152 overexpression increases the sensitivity of GBC cells to gemcitabine, whereas silencing RNF152 has the opposite effect. Fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency increases the lysosomal localization of p18 and increases mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity. RNF152 suppresses mTORC1 activity to inhibit glycolysis and enhance gemcitabine sensitivity in GBC., Competing Interests: The authors declare no conflict of interest, (© 2024 The Authors.)

Background: Cholangiocarcinoma is a poorly prognostic malignant tumor, and the metastatic stage of cancer is not an early stage when diagnosed. Lymph node metastasis is common in the early stage. Ribosomal receptor for activated C-kinase 1 (RACK1) has found involved in the oncogenesis of various tumors and in the epithelial-mesenchymal transition (EMT). Nevertheless, its role in cholangiocarcinoma remains unknown., Material and Methods: The possible correlation between RACK1 and tumor prognosis was analyzed in cholangiocarcinoma patients. The GEO and TCGA databases were used to evaluate the level of RACK1 in cholangiocarcinoma. The RBE and HCCC-9810 cell lines were used to examine the effects of RACK1 in the behavior of tumor cells in vitro., Results: The Kaplan-Meier analysis indicated that low expression of RACK1 was associated with poor prognosis and RACK1 was negatively related to lymph node metastasis, which were verified in databases TCGA and GEO; downregulation of RACK1 via RNA interference correlated with changes in the expression of EMT biomarkers and promoted the migration of cholangiocarcinoma cell lines., Conclusion: The protein expression of RACK1 is significantly higher in cholangiocarcinoma tissues than in peritumoral tissues, however, the high RACK1 expression indicates better overall survival and less risk for lymph node metastasis. In vitro , RACK1 may suppress the migratory ability of cholangiocarcinoma cells by inhibiting EMT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Published by Elsevier Ltd.)

Although single-metal-site (SMS) catalysts have long been explored for the electrochemical CO 2 reduction reaction (EC-CO 2 RR), the reactivity and selectivity of SMS catalysts remain rather low due to the competing hydrogen evolution reaction (HER). To improve the selectivity, in this work, a novel intermetallic particle of CuNi is decorated on the N-doped carbon substrate, which was first precisely fabricated by scarifying the bimetal-doped metal-organic framework (MOF). Thanks to the neighboring synergistic functions of Cu and Ni sites, CuNi/NC prominently boosts the electroreduction of CO 2 , far more than the SMS catalysts of Cu/NC and Ni/NC. Further, CuNi/NC presents superior selectivity toward CO with faradaic efficiency over a wide range of potentials (surpassing 90% at 0.6-1.0 V vs RHE, up to 98% at 0.6 V vs RHE) and excellent durability. The experimental results and theoretical calculations reveal that the Ni species can be highly activated due to the neighboring Cu species, which considerably facilitates the formation of an intermediate of COOH* and consequently enhances the selectivity of the reduction of CO 2 to CO. This work paves a general way to precisely fabricate catalysts with multiple metal species and also demonstrates the significant synergetic efficiency between the neighboring sites to improve the catalytic performance.

The human body comprises various tubular structures that have essential functions in different bodily systems. These structures are responsible for transporting food, liquids, waste, and other substances throughout the body. However, factors such as inflammation, tumors, stones, infections, or the accumulation of substances can lead to the narrowing or blockage of these tubular structures, which can impair the normal function of the corresponding organs or tissues. To address luminal obstructions, stenting is a commonly used treatment. However, to minimize complications associated with the long-term implantation of permanent stents, there is an increasing demand for biodegradable stents (BDS). Magnesium (Mg) metal is an exceptional choice for creating BDS due to its degradability, good mechanical properties, and biocompatibility. Currently, the Magmaris ® coronary stents and UNITY-B TM biliary stent have obtained Conformité Européene (CE) certification. Moreover, there are several other types of stents undergoing research and development as well as clinical trials. In this review, we discuss the required degradation cycle and the specific properties (anti-inflammatory effect, antibacterial effect, etc.) of BDS in different lumen areas based on the biocompatibility and degradability of currently available magnesium-based scaffolds. We also offer potential insights into the future development of BDS.

Herein, an effective Pd/NHS catalyst has been designed and facilely synthesized with extraordinary CO 2 fixation performance, which is superior to that of Pd/NS catalysts, owing to the hollow structures facilitating mass transfer and product release.

Ethnopharmacological Relevance: Inflammation plays a critical role during benign prostatic hyperplasia (BPH) development. Danzhi qing'e (DZQE) decoction is a traditional Chinese medicine that has been widely used for estrogen and androgen-related diseases. However, its effect on inflammation-related BPH remains unclear., Aim of the Study: To investigate the effect of DZQE on inhibition of inflammation-related BPH, and further identify the possible mechanism involved., Methods and Materials: Experimental autoimmune prostatitis (EAP)-induced BPH was established and then 2.7 g/kg of DZQE was administrated orally for 4 weeks. The prostate sizes, weights and prostate index (PI) values were recorded. Hematoxylin and eosin (H&E) was performed for pathological analyses. Macrophage infiltrate was evaluated by Immunohistochemical (IHC). The inflammatory cytokine levels were measured by Rt-PCR and ELISA methods. The phosphorylation of ERK1/2 was examined by Western blot. The expression differences of mRNA expressions between EAP-induced and oestrogen/testosterone (E2/T)-induced BPH was investigated by RNA sequencing analyses. In vitro, human prostatic epithelial BPH-1 cells were stimulated with the conditioned medium from monocyte THP-1-derived M2 macrophages (M2CM), followed by treatment of Tanshinone IIA (Tan IIA), Bakuchiol (Ba), ERK1/2 antagonist PD98059 or ERK1/2 agonist C6-Ceramide. The ERK1/2 phosphorylation and cell proliferation were then detected by Western blotting and CCK8 assay., Results: DZQE significantly inhibited the prostate enlargement and decreased PI value in EAP rats. Pathological analysis showed that DZQE alleviated prostate acinar epithelial cell proliferation by decreasing and reduction of CD68 + and CD206 + macrophage infiltration in the prostate. The levels of cytokines TNF-α, IL-1β, IL-17, MCP-1, TGF-β, and IgG in EAP rats' prostate or serum were significantly suppressed by DZQE as well. Moreover, mRNA sequencing data showed that the expressions of inflammation-related genes were elevated in EAP-induced BPH but not in E2/T-induced BPH. ERK1/2-related genes expression has been found in both E2/T and EAP-induced BPH. ERK1/2 is one of the core signal pathways involved in EAP-induced BPH, which was activated in EAP group but inactivated in DZQE group. In vitro, two active components of DZQE Tan IIA and Ba inhibited M2CM-induced BPH-1 cell proliferation, similarly to ERK1/2 inhibitor PD98059 did. Meanwhile, Tan IIA and Ba inhibited M2CM-induced ERK1/2 signal activation in BPH-1 cells. When re-activated the ERK1/2 by its activator C6-Ceramide, the inhibitory effects of Tan IIA and Ba on BPH-1 cell proliferation were blocked., Conclusion: DZQE suppressed inflammation-associated BPH via regulation of ERK1/2 signal by Tan IIA and Ba., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Context : In the event of accidental trauma, incurable disease and public health emergencies, young adults are unable to participate in their own medical decisions, family members face the huge decision-making pressure and medical resources of the society were unevenly distributed. Objective : The purposes of this study is to investigate the Advanced Care Planning (ACP) acceptance and examine its influencing factors using sequential explanatory mixed methods in order to provide a basis for the formulation of later interventions. Methods : A cross-sectional study of young adults (N = 785) and 12 other young adults from two other communities were investigated from January 2021 to February 2022. Descriptive statistics and multiple linear regressions were conducted. Content analysis was performed on the qualitative data. Results : The primary factors that contributed to the acceptance of ACP were the natural acceptance of death, being female, having a high level of education, having a loved one diagnosed with a chronic disease, and having heard of ACP. Among young adults, the acceptance of ACP may be impeded by a fear of the unknown nature of death, a poor understanding of ACP, and family-led decision-making. Discussion : Our study found that 77.1% had not heard of ACP before participating in the study and showed potential to accept ACP-related interventions. The study highlighted the importance of implementing regular young adult education courses, promoting routine ACP knowledge, individualized education, discussing family member's disease experiences, conducting family meetings, and identifying young adult responsibilities and roles in implement ACP for young adults in China.

Cadmium ion (Cd(II)) is a pernicious environmental pollutant that has been shown to contaminate agricultural lands, accumulate through the food chain, and seriously threaten human health. At present, Cd(II) monitoring is dependent on centralized instruments, necessitating the development of rapid and on-site detection platforms. Against this backdrop, the present study reports on the development of a fluorometric aptasensor designed to target Cd(II), which is achieved through the integration of strand displacement amplification (SDA) and CRISPR/Cas12a. In the absence of Cd(II), the aptamer initiates SDA, resulting in the generation of a profusion of ssDNA that activates Cas12a, leading to a substantial increase in fluorescence output. Conversely, the presence of Cd(II) curtails the SDA efficiency, culminating in a significant reduction in fluorescence output. The proposed approach has been demonstrated to enable the selective detection of Cd(II) at concentrations of 60 pM, with the performance of the aptasensor validated in real water and rice samples. The proposed platform based on aptamer-target interaction holds immense promise as a signal-amplified and precise method for the detection of Cd(II) and has the potential to transform current hazard detection practices in food samples., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

14-3-3 proteins are ubiquitous adapters combining with phosphorylated serine/threonine motifs to regulate multiple cellular processes. As a negative regulator, 14-3-3 proteins could sequester the phosphorylated YAP1 in cytoplasm to inhibit its activity. In this study, we identified the K50 acetylation (K50ac) of 14-3-3ε protein and investigated its roles and mechanism in cholangiocarcinoma progression. The NAD (+)-dependent protein deacetylases inhibitor, NAM treatment significantly up-regulated the K50ac of 14-3-3ε. K50R mutation resulted in the decrease of K50ac of 14-3-3ε. The K50ac of 14-3-3ε was reversibly mediated by PCAF acetyltransferase and sirt1 deacetylases. K50ac had no obvious effect on the protein stability of 14-3-3ε, but inhibited the combination of 14-3-3ε with phosphorylated YAP1, which resulted in the activation of YAP1 in cholangiocarcinoma. K50R significantly decreased cholangiocarcinoma cell proliferation in vitro and the growth of tumor xenograft in vivo compared with WT (wild type) 14-3-3ε. The level of K50ac were higher in cholangiocarcinoma tissues accompanied by the accumulation of YAP1 in nuclear than para-carcinoma tissues. Our study revealed the underlying mechanism of K50ac of 14-3-3ε and its roles in cholangiocarcinoma, providing a potential targeting for cholangiocarcinoma therapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Balloon Analog Risk Task (BART) is increasingly used to assess risk-taking behavior and brain function. However, the brain networks underlying risk-taking during the BART and its reliability remain controversial. Here, we combined the activation likelihood estimation (ALE) meta-analysis with both task-based and task-free functional connectivity (FC) analysis to quantitatively synthesize brain networks involved in risk-taking during the BART, and compared the differences between adults and adolescents studies. Based on 22 pooled publications, the ALE meta-analysis revealed multiple brain regions in the reward network, salience network, and executive control network underlying risk-taking during the BART. Compared with adult risk-taking, adolescent risk-taking showed greater activation in the insula, putamen, and prefrontal regions. The combination of meta-analytic connectivity modeling with task-free FC analysis further confirmed the involvement of the reward, salience, and cognitive control networks in the BART. These findings demonstrate the core brain networks for risk-taking during the BART and support the utility of the BART for future neuroimaging and developmental research., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H 2 S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated by KRAS mutation to promote CSE transcription. An Nrf2 binding site (‒47/‒39 bp) in the CSE promoter is verified. CSE overexpression and the addition of NaHS after Nrf2 knockdown or inhibition by brusatol decreases ROS levels and rescues cell proliferation. Our study reveals the regulatory mechanism of intracellular ROS levels in KRAS mutant pancreatic cancer cells, which provides a potential target for pancreatic cancer therapy.

For a hydrogenation heat exchanger operating under severe working conditions such as high temperature, high pressure and a hydrogen environment, perforation accidents caused by NH 4 Cl corrosion occur frequently. However, few reports on the effect of hydrogen on the corrosion behavior of metal materials in NH 4 Cl aqueous solution have been published. In this paper, X-ray photoelectron spectroscopy (XPS), electrochemical dynamic potential polarization, electrochemical impedance spectroscopy (EIS), Mott-Schottky (M-S) curves and scanning electron microscopy (SEM) were used to study the effect of electrochemical hydrogen charging (EHC) on the corrosion behavior of 321 stainless steel in an NH 4 Cl solution environment. The results show that: (1) hydrogen can change the structure and chemical composition of 321 stainless steel passive film and promote the conversion of metal oxide to hydroxide. At the same time, it can reduce the stability of the passive film. (2) Hydrogen can increase the thermodynamic and kinetic tendency of corrosion reaction and cooperate with Cl - to promote the occurrence of pitting corrosion.